CALCIUM MOVEMENTS IN EXCITATION-CONTRACTION COUPLING

动作电位到肌肉收缩的转导（EC耦合）是 细胞膜事件和代谢之间的快速通信的例子 状态 在许多系统中，这种耦合的中心信使是 钙，在肌肉中从肌浆网（SR）释放 来激活收缩蛋白 我们的目标是定量地了解 这些运动。 SR的释放通道由在200 ℃下的电位变化控制。 血浆和T-管膜在一个不理解的方式，涉及一个 电压传感器在T-管状膜和一个未知的机制， 电压传感器和释放通道之间的通信（T-SR耦合）。 我们可以测量EC耦合步骤的主要变量：电荷 与电压传感器相关的运动电流， 肌浆[Ca]和Ca流通过释放通道。 横向 肌肉的管状膜有一个（“慢”）CA通道，未知 功能性作用，数量众多。 我们的研究结果表明，慢钙 通道与电荷运动和Ca释放密切相关。 我们计划 为了研究电荷运动，寻求一个统一的模型， 组件，以阐明其与CA版本的关系。 我们将在 详细说明慢钙通道和EC偶联事件的药理学 为了验证慢钙通道参与EC的假说， 偶合器. 如果是这种情况，将寻求在T-SR耦合中的作用 Ca通道和通道携带的电流。 我们会研究 在人工双层膜上重建慢钙通道， 在更好定义的离子条件下表征其性质。 我们将 比较了三种T-SR耦合机制的优点：a 机械连接、钙和IP 3作为发射器。 会来做这项工作 在细胞内介质中引入选择性干扰 所提出的机制，包括快速钙缓冲和阻断剂， IP 3代谢。 钙的释放及其被蛋白质和SR泵去除是主要的 Ca调节中的通量。 一种助熔剂的研究进展 产生并需要更多关于对方的知识。 的关系 在CA去除通量和由CA去除通量产生的固有光信号之间， 肌肉将被研究。 钙结合蛋白Pravalbumin将是 引入肌肉纤维以测试其在内在信号中的作用， 最终关闭了钙的循环 动作

The transduction of action potential to muscle contraction (EC coupling) is an example of fast communication between cell membrane events and metabolic state. As in many systems, the central messenger of this coupling is calcium, which in muscle is released from the Sarcoplasmic Reticulum (SR) to activate contractile proteins. Our goal is to understand quantitatively these Ca movements. The release channels of the SR are controlled by changes in potential at the plasma and T-tubular membrane in an ill-understood way, involving a voltage sensor in the T-tubular membrane and an unknown mechanism of communication between voltage sensor and release channel (T-SR coupling). We can measure the main variables of the EC coupling steps: charge movement currents associated to the voltage senor, the rapid change in myoplasmic [Ca] and Ca flux through the release channel. The transverse tubular membrane of muscle has a ('slow') CA channel, of no known functional role, in large numbers. Our results suggest that the slow Ca channel is intimately related to charge movement and Ca release. We plan to study charge movement, seeking a unified model of its many described componennts to clarify its relationship to CA release. We will compare in detail the pharmacology of the slow Ca channel and the EC coupling events to test the hypothesis that the slow Ca channel is involved in EC coupling. If this is the case a role in T-SR coupling will be sought for the Ca channel and the current carried by the channel. We will study the slow Ca channel reconsituted in artificial bilayer membranes to characterize its properties in better defined ionic conditions. We will compare the merits of three proposed mechanism of T-SR coupling: a mechanical link, calcium, and IP3 as a transmitter. This will be done by introducing changes in the intracellular medium that selectively interfere with the proposed mechanisms, including a fast Ca buffer and a blocker of IP3 metabolism. Release of Ca and its removal by proteins and the SR pump are the main fluxes involved in Ca regulation. Progress in the study of one flux generates and requires more knowledge about the other. The relationship between CA removal fluxes and an intrinsic optical signal generated by the muscle will be studied. The Ca binding protein pravalbumin will be introduced into muscle fibers to test its role in the intrinsic signal and in the process of removal that eventually closes the cycle of calcium movements.